Flecainide combination and controlled-release formulations for treating heart diseases

Abstract

The invention relates to flecainide formulations and to methods of their administration. Specifically, the invention relates to combination formulations of a flecainide and a rate control agent for treating various heart diseases, and to controlled-release flecainide formulations, including such formulations in combination with rate control agents.

1 . A pharmaceutical formulation comprising a flecainide in combination with a rate control agent, wherein the rate control agent comprises a β blocker, and wherein the β blocker is metoprolol. 
     
     
         2 .- 11 . (canceled) 
     
     
         12 . The pharmaceutical formulation of  claim 1 , wherein the flecainide comprises a flecainide acetate. 
     
     
         13 . The pharmaceutical formulation of  claim 1 , configured in a dosage form selected from once daily, twice daily, once every two days, once every three days, once every four days, once every five days, once every six days, and once weekly. 
     
     
         14 . The pharmaceutical formulation of  claim 1 , wherein the flecainide is present in an amount of about 50 to about 500 mg. 
     
     
         15 . The pharmaceutical formulation of  claim 1 , wherein the rate control agent is present in an amount of about 50 to about 500 mg. 
     
     
         16 . The pharmaceutical formulation of  claim 1 , wherein the formulation further comprises an effective amount of one or more additional therapeutic agents. 
     
     
         17 . A method of treating atrial fibrillation, atrial flutter, and/or supraventricular tachycardia (SVT) in a subject, the method comprising administering the pharmaceutical formulation of  claim 1  to a subject in need thereof. 
     
     
         18 .- 35 . (canceled) 
     
     
         36 . A controlled-release pharmaceutical formulation comprising a flecainide and a controlled-release excipient. 
     
     
         37 . The controlled-release pharmaceutical formulation of  claim 36  wherein the controlled-release formulation comprises a once daily sustained-release formulation. 
     
     
         38 . The controlled-release pharmaceutical formulation of  claim 36 , wherein the controlled-release excipient is configured to modify a dissolution profile of said sustained-release flecainide. 
     
     
         39 . The controlled-release pharmaceutical formulation of  claim 38 , wherein the controlled-release excipient comprises at least one selected from hydroxypropyl methylcellulose (HPMC), hydroxyethylcellulose, hydroxypropylcellulose (HPC), methylcellulose, ethylcellulose, cellulose acetate butyrate, cellulose acetate phthalate, hydroxypropylmethyl cellulose phthalate, microcrystalline cellulose, corn starch, polyethylene oxide, polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), cross-linked PVP, polyvinyl acetate phthalate, polyethylene glycol, zein, poly-DL-lactide-co-glycolide (PLGA), dicalcium phosphate, calcium sulfate, and mixtures thereof. 
     
     
         40 . The controlled-release pharmaceutical formulation of  claim 36 , wherein said flecainide is a flecainide acetate. 
     
     
         41 . The controlled-release pharmaceutical formulation of  claim 36 , further comprising a filler wherein said filler comprises at least one selected from acetyltriethyl citrate (ATEC), acetyltri-n-butyl citrate (ATBC), aspartame, lactose, alginates, calcium carbonate, carbopol, carrageenan, cellulose, cellulose acetate phthalate, croscarmellose sodium, crospovidone, dextrose, dibutyl sebacate, ethylcellulose, fructose, gellan gum, glyceryl behenate, guar gum, lactose, lauryl lactate, low-substituted hydroxypryopl cellulose (L-HPC), magnesium stearate, maltodextrin, maltose, mannitol, methylcellulose, microcrystalline cellulose, methacrylate, sodium carboxymethylcellulose, polyvinyl acetate phthalate (PVAP), povidone, shellac, sodium starch glycolate, sorbitol, starch, sucrose, triacetin, triethylcitrate, vegetable based fatty acid, xanthan gum, and xylitol. 
     
     
         42 . The controlled-release pharmaceutical formulation of  claim 36 , configured in a dosage form selected from once daily, twice daily, once every two days, once every three days, once every four days, once every five days, once every six days, and once weekly. 
     
     
         43 . The controlled-release pharmaceutical formulation of  claim 36 , wherein the flecainide is present in an amount of about 50 to about 500 mg. 
     
     
         44 . The controlled-release pharmaceutical formulation of  claim 36 , wherein the formulation further comprises an effective amount of one or more other therapeutic agents. 
     
     
         45 . The controlled-release pharmaceutical formulation of  claim 44 , wherein at least one of said other therapeutic agent comprises a rate control agent. 
     
     
         46 . The controlled-release pharmaceutical formulation of  claim 45 , wherein said rate control agent comprises a beta blocker. 
     
     
         47 . The controlled-release pharmaceutical formulation of  claim 45 , wherein said rate control agent comprises a calcium channel blocker. 
     
     
         48 . The controlled-release pharmaceutical formulation of  claim 45 , wherein said rate control agent comprises a digitalis. 
     
     
         49 . A method of treating atrial fibrillation, atrial flutter, and/or supraventricular tachycardia (SVT) in a subject, comprising administering the pharmaceutical formulation of  claim 36  to a subject in need thereof. 
     
     
         50 .- 53 . (canceled) 
     
     
         54 . The controlled-release pharmaceutical formulation of  claim 36 , wherein the flecainide is dispersed in a wax matrix. 
     
     
         55 . The controlled-release pharmaceutical formulation of  claim 36 , wherein the flecainide is dispersed in a polymer matrix. 
     
     
         56 . The controlled-release pharmaceutical formulation of  claim 36 , wherein the flecainide is dispersed in an encapsulated form.